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Trial · Interventional

TerminatedPhase 3Results postedRegistry data

GnRH-a for Ovarian Protection During CYC Therapy for Rheumatic Diseases

Short name LUPRON

NCTNCT01257802 (opens ClinicalTrials.gov in a new tab)Other idHUM00043071Other id5R01HD066139

Overview

Status
Terminated
Phase
Phase 3
Enrollment
14 participants (actual)
Sponsor
Joseph Mccune · Other
Design
Randomized · Double masking
Countries
1 country

United States

Start
May 2011
Primary completion
Oct 2015
Completion
Nov 2015
First posted
10 Dec 2010 (estimated)
Last update posted
27 Jun 2017
Conditions
Lupus Erythematosus, Systemic · Systemic Vasculitis · Isolated Angiitis of Central Nervous System · Lung Disease With Systemic Sclerosis · Lung Disease Interstitial Diffuse

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201120122013201420152016
  1. Ph 3

    LUPRON

    NCT01257802

    May 2011 to Nov 2015

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The purpose of this study it to determine whether the use of a gonadotropin releasing hormone (GnRH)-agonist (depot-leuprolide acetate) during cyclophosphamide (CYC) therapy in women with rheumatic diseases will provide greater ovarian protection than placebo.

Interventions

  • depot leuprolide acetate 3.75 mgDrug
  • PlaceboDrug

Arms2

  • Active comparator

    LUPRON

    Monthly depot leuprolide acetate 3.75 mg injection during cyclophosphamide administration. First dose of study drug given at least 10 days before following dose of cyclophosphamide if cyclophosphamide is given in biweekly or monthly boluses

  • Placebo comparator

    Placebo

    Monthly placebo injection during cyclophosphamide administration. First dose of study drug given at least 10 days before following dose of cyclophosphamide if cyclophosphamide is given in biweekly or monthly boluses.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Anti-mullerian Hormone (AMH) Measured as a Continuous Variable, Specifically Assessing the Intra-person Change From Study Entry (Day 0) to 6-month Post-intervention Visit

    Time frame · Day 0 to 6-month post-intervention visit

    Registry description

    AMH was quantified in vitro a commercially available enzyme linked immunosorbent assay (ELISA) (Beckman Coulter; Marseille, France) was used for in vitro quantitative measurement of serum AMH.

Secondary outcomes(4)
  1. Count of Patients With AMH of ≤1.0 ng/mL vs >1 ng/mL,

    Time frame · baseline and 6 months

    Registry description

    AMH level ≤1.0 predicts onset of menopause within 5 years in normal women

  2. Number of Participants With Either an AMH Level of >1 ng/mL OR Antral Follicle Count of >4.

    Time frame · baseline and 6 months

    Registry description

    An AMH level of \>1 ng/ml and/or an antral follicle count of \>4 in either ovary is a strong predictor of residual ovarian function

  3. Mean Antral Follicle Count (AFC)

    Time frame · baseline and 6 months

    Registry description

    Mean antral follicle count (AFC) is the average number of follicles counted in each of 2 ovaries

  4. Mean Ovarian Volume.

    Time frame · baseline and 6 months

    Registry description

    Mean ovarian volume reflects the preservation of ovarian tissue despite exposure to cyclophosphamide; reduced ovarian size is documented in cyclophosphamide treated patients

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Day 0 to 6-month post-intervention visit

Anti-mullerian Hormone (AMH) Measured as a Continuous Variable, Specifically Assessing the Intra-person Change From Study Entry (Day 0) to 6-month Post-intervention Visit

GroupValue (ng/ml)Spread
LUPRON2.071.92
Placebo3.874.00
Secondary and other outcome results(4)
Secondary outcomeCount of participants· baseline and 6 months

Count of Patients With AMH of ≤1.0 ng/mL vs >1 ng/mL,

GroupValue (Participants)
LUPRON3
PLACEBO6
Secondary outcomeCount of participants· baseline and 6 months

Number of Participants With Either an AMH Level of >1 ng/mL OR Antral Follicle Count of >4.

GroupValue (Participants)
LUPRON4
PLACEBO6
Secondary outcomeMean· baseline and 6 months

Mean Antral Follicle Count (AFC)

GroupValue (# of ovarian follicles)Spread
LUPRON10.39.29
PLACEBO14.412.4
Secondary outcomeMean· baseline and 6 months

Mean Ovarian Volume.

GroupValue (cubic centimeters)Spread
LUPRON9.592.69
PLACEBO7.683.50

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
LUPRONdepot leuprolide acetate 3.75 mg: Monthly depot leuprolide acetate 3.75 mg vs placebo during cyclophosphamide administration. First dose of study drug given at least 10 days before following dose of cyclophosphamide if cyclophosphamide is given in biweekly or monthly boluses0 / 61 / 65 / 6
Placebodepot leuprolide acetate 3.75 mg: Monthly depot leuprolide acetate 3.75 mg vs placebo during cyclophosphamide administration. First dose of study drug given at least 10 days before following dose of cyclophosphamide if cyclophosphamide is given in biweekly or monthly boluses Placebo: Monthly placebo during cyclophosphamide administration. First dose of study drug given at least 10 days before following dose of cyclophosphamide if cyclophosphamide is given in biweekly or monthly boluses0 / 81 / 85 / 8

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
Female
Age
from 18 Years up to 40 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
1. Female, post menarche, not menopausal 2. Ages 18-40 years inclusive at enrollment 3. Diagnosis consistent with a rheumatic or autoimmune disease requiring 3-6 months of daily or intermittent cyclophosphamide therapy. This may include, but is not limited to: * Systemic lupus * Sjogren's syndrome * Systemic vasculitis * Isolated vasculitis of the central nervous system * Other autoimmune neurologic diseases requiring cyclophosphamide including transverse myelitis, peripheral neuropathies, multiple sclerosis, neuromyelitis optica, and retinal vasculitis * Behcet's syndrome * Scleroderma * Inflammatory myositis * Interstitial lung disease, other autoimmune pulmonary diseases requiring cyclophosphamide * Overlap connective tissue diseases not precisely fitting the above definitions clearly requiring cyclophosphamide for severe immune mediated organ damage * Rheumatoid vasculitis 4. Patients will have planned cyclophosphamide treatment according to any one of the following regimens: * 3 to 6 months of daily oral cyclophosphamide: Lupron/placebo must be given within four (4) weeks of initiation of daily cyclophosphamide. * The Eurolupus regimen consisting of 6 fortnightly biweekly boluses of 500 mg cyclophosphamide: First dose of Lupron/placebo must be given 10 days prior to the second dose of cyclophosphamide * 3 to 6 monthly boluses of cyclophosphamide by the NIH regimen: First dose of Lupron/placebo must be given 10 days prior to the second dose of cyclophosphamide 5. A satisfactory plan for contraception consistent with cyclophosphamide administration (when appropriate: depot progestins, IUD, combination oral contraception and/or dual barrier contraception). Exclusion Criteria: 1. Symptoms consistent with ovarian failure based on gynecologic evaluation and confirmatory laboratory testing 2. Prior unilateral or bilateral oophorectomy 3. Cervical intraepithelial neoplasia (CIN 2, or more severe), that has not been adequately evaluated or is not being adequately treated 4. Contraindications to use of GnRH-a (e.g., undiagnosed abnormal uterine bleeding) 5. Prior adverse or allergic reaction to GnRH-a 6. A history of severe psychiatric disorders, particularly severe depression that is currently not adequately treated 7. History of significant noncompliance with medical treatment 8. Patients with major risk factors for decreased bone mineral content such as chronic alcohol and/or tobacco use, strong family history of osteoporosis, or chronic use of drugs that can reduce bone mass such as anticonvulsants that have not already been addressed with appropriate measures to preserve bone mass. 9. Pregnant or breastfeeding 10. Significant thrombotic event requiring treatment that will not have received appropriate therapy for at least 4 weeks before initiation of study drug.

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